TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC.


March 2021
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Reporting on sex and gender Female Population characteristics 28 primary human breast cancer tissue samples and corresponding adjacent normal tissues were from female TNBC patients. The information of patients are summarized in Supplementary Table1.

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We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material, system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response. human, mouse; WB (1:1000), IP (1:100) the antibody specificity was tested by TMEM25 knockout human MDA-MB-231 cells and mouse 4T1 cells (our manuscript Fig.5a-b Western blot analysis of mouse NIH 3T3 whole cell lysate (instruction from manufacturer's website). Goat anti-Rabbit IgG (H+L) Secondary Antibody, HRP ThermoFisher cat# 31460 Western blot analysis was performed on whole cell extracts of human A549 and Hep G2 cells. The blots were probed with Anti-CacyBP Rabbit Polyclonal Antibody and detected by chemiluminescence using Goat anti-Rabbit IgG (H+L) Secondary Antibody, HRP conjugate (instruction from manufacturer's website). Goat anti-Mouse IgG (H+L) Secondary Antibody, HRP ThermoFisher cat# 31430: Western blot analysis was performed on whole cell extracts of human K-562 and U87-MG. The blots were probed with Anti-SOD2 Mouse Monoclonal Antibody and detected by chemiluminescence using Goat anti-Mouse IgG (H+L)

March 2021
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March 2021
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